Sirolimus for pure red cell aplasia relapsed/refractory to cyclosporine A

JRCT ID: jRCT2031240482

Registered date:13/11/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: acquired chronic pure red cell aplasia
• Date of first enrollment: 01/12/2024
• Target sample size: 30
• Study type: Interventional
• Intervention(s): a double-blinded placebo controlled clinical trial of sirolimus for PRCA

Outcome(s)

Primary Outcome

Difference in hemoglobin (Hb) levels between baseline (week 0) and 24 weeks after study treatment or at the time of interruption or discontinuation (at week 24)
Hemoglobin (Hb) values will be measured at least 14 days after the last red blood cell transfusion.

Secondary Outcome

(1) Hemoglobin (Hb) values: comparison of Hb values obtained at baseline (week 0), 12 weeks and 24 weeks after study treatment in a mixed effects model (MMRM) adjusted for baseline values and the allocation factor, Hb ( <7.3 or >=7.3)
(2) Hb level: Comparison of change from baseline (week 0) at 12 weeks after the start of study treatment.
(3) Reticulocyte count: Comparison of change from baseline (Week 0) at Weeks 12 and 24 after the start of study treatment.
The reticulocyte count will be measured at least 14 days after the last erythrocyte transfusion.
(4) RBC transfusions: comparison of the frequency of RBC transfusions (units/week) in the 10 weeks before study treatment, the 10 weeks from 15 to 24 weeks after study treatment, and the 10 weeks from 43 to 52 weeks after study treatment.
(5) Group comparison of red blood cell transfusion volume from baseline (week 0) to 24 weeks after start of study treatment
(6) Response rate: comparison of the percentage of patients with an increase in Hb level of 1.5 g/dL or more at 24 weeks after the start of study treatment between groups
(7) Trends in Hb levels (baseline (week 0), 12, 24, 36, 48, and 52 weeks after start of study treatment)
(8) Changes in reticulocyte count (baseline (week 0), 12, 24, 36, 48, and 52 weeks after study treatment)
(9) Changes in whole blood trough concentration (description only)
(10) FACIT-Fatigue Scale: comparison of change from baseline (week 0) at 24 weeks after start of study treatment

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable

Include criteria

(1) Patients diagnosed as acquired chronic pure red cell aplasia (PRCA) in accordance with a diagnostic criteria of the clinical guide for the treatment of pure red cell aplasia, revised in 2022, and the diagnosis being either idiopathic pure red cell aplasia, thymoma-associated pure red cell aplasia, or large granular lymphocytic leukemia-associated pure red cell aplasia
(2) Patients with hemoglobin (Hb) llevel ess than 9 g/dL at screening
(3) Patients with one or more of the following at the time of the informed consent
1) patients with PRCA having not responded after at least 3 month of treatment with a regular dose of cyclosporine (non-responding patients)
2) patients intolerant to at least 3 month of treatment for PRCA with cyclosporine due to its adverse effects such as renal impairment and hypertension in the past (intolerant patients)
3) patients with one of the contraindications for cyclosporine such as renal impairment or hypertension
4) patients with PRCA, once having responded to cyclosporin, having relapsed during its tapering or after its withdrawal (relapsed patients)
(4) 18 years of age or older at the time of informed consent
(5) being fully informed about participating this clinical trial and giving written informed consent based on their free will

Exclude criteria

(1) female patient during pregnancy or breastfeeding period at the time of screening. Or a man and woman who do not consent to contraception from the time of consent until 12 weeks after the last dose of the investigational drug.
(2) having respiratory symptoms of interstitial pneumonia, such as coughing, dyspnia, or fever
(3) past history treatment with sirolimus or other mTOR inhibitors
(4) having been on immunosuppressive treatment for PRCA, such as cyclosporin, steroid, or cyclophosphamide, within 6 weeks of the time of the informed consent. Except steroid treatment for a medical condition other than PRCA as long as it is equivalent dose of less than 10 mg of prednisolon
(5) being anticipating a major surgery requiring blood transfusion between 2 weeks prior to and 53 weeks after the first dose of the investigational drug.
(6) having been a recepient of hematopoietic transplantation, or ancitipation a transplantation during the test period
(7) platelet count less than 75,000/mcL, neutrophil count less than 1,000/mcL, or white blood cell count less than 2,500/mcL at the time of screeing
(8) Aspartate aminotransaminase or alanine transaminase higher than 3 time of upper limit of normal range at the time of screening
(9) eGFR less than 30 mL/min/1.73m2 at the time of screening
(10) hypersensitive to any ingredients of investigational drug or sirolimus, including additives
(11) being in immunodeficient state such as having HIV or other primary immunodeficiency
(12) having tested positive for either 1) HBs antigen, 2) HBs antibody or HBc antibody and HBV-DNA, 3) active HCV infection
(13) having a past history of mycobacterium tuberculosis infection
(14) having a past history of malignancy within 2 years prior to informed consent
(15) having a past histor of thymectomy within 2 years prior to informed consent
(16) having an active infectious disease
(17) having a history of intoxication of illegal drugs or alcohol within 5 years prior to informed consent, or having a history of abuse of either of them withing a year of the infomed consent
(18) being participating in other clincal trial with in 30 days of the informed consent
(19) miscellaneous

Related Information

• Primary Sponsor: Nakazawa Hideyuki
• Source(s) of Monetary Support: Nobelpharma Co., Ltd.,Japan Agency for Medical Research and Development